Basic cell sciences denote that whenever a cell divides, there is a chance for DNA mutation to take place during the replication process. Consequently, these mutations can lead to cancer development.

With that understanding in place, larger and long-lived animals have more cells—and undergo frequent and rapid cell divisions. Thus, they should develop cancer at a higher rate than smaller and short-lived animals that have fewer cells dividing over a shorter period. However, this was proven to be untrue.

In 1977, Sir Richard Peto realised that humans develop cancer at a similar rate to mice, defying the above theory because humans have 1,000 times as many cells—and live 30 times as long. A similar phenomenon is seen in elephants that are 100 times larger than humans and live 60 to 70 years—but have extremely low rates of cancer.

Evolution served as the answer to this mind-boggling conundrum. Peto proposed that as humans evolved to grow larger and persevere throughout evolutionary history—with more cell division taking place over a longer period— humans also evolved to resist cancer. This piece of research has become known as Peto’s Paradox.

The tumour suppressor gene, TP53


Dr Carlo Maley, an evolutionary and cancer biologist says that cancer medicine has been so focused on the molecular particulars of the disease—not taking into account that elephants and whales manage to avoid cancer without vitamin supplements or chemotherapy regimens. He posed a perplexing question, “How did evolution solve this problem that’s vexing humans?”

The key to understanding the upper-hand elephants have over humans lies in the tumour suppressor gene, TP53. One study to investigate this paradox was done by the University of Utah in collaboration with Dr Maley. Patients with Li- Fraumeni Syndrome (LFS), who are missing their TP53 genes and have an elevated rate of cancer, were studied together with DNA from elephants and healthy humans.

The elephant DNA was broken down with radiation and studied to assess the time taken for reparation. It concluded that the rate of DNA repair was similar between elephant and human cells but, interestingly, after elephant cells were exposed to radiation, more cells underwent apoptosis compared to human cells.

The study concluded that the amount of apoptosis correlated with the number of TP53 genes. It also followed the same pattern of lifetime cancer risk whereby elephants had a 5% risk, humans had a 50% risk and patients with LFS had a 90% risk. With the prior knowledge of elephants having 40 TP53 genes, healthy humans having just 2 and those with LFS having 1 TP53 gene, it could be concluded that the increase in quantity of TP53 genes makes the cells more effective at removing pre-cancer cells that could develop to form cancer.

Significance of research to humans


The research showed that elephant cancer resistance was probably due to the rapid removal of pre-cancerous cells with DNA damage. Further research is being done to better understand the mechanism of TP53 in elephants and its application in patients with cancer and patients at risk of cancer in the future.

Potential treatment for cancer or cancer prevention could be conjured up with this knowledge basis. Researchers believe medicine could eventually bring about a compound that replicates the TP53-rich environment in elephants or, somehow, discover a method to insert the elephant TP53 gene into humans. The study, thus far, has proved to be significant to human cancer research besides potentially saving the lives of elephants, as they are evidently important research animals. MIMS

Read more:
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Epigenetic drugs: The promise of future precise cancer treatments
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Sources:
http://theconversation.com/what-elephants-teach-us-about-cancer-prevention-76237
http://www.nature.com/news/massive-animals-may-hold-secrets-of-cancer-suppression-1.12258
http://www.newsweek.com/2015/10/16/researchers-studying-elephants-improve-cancer-treatment-380822.html
http://jamanetwork.com/journals/jama/fullarticle/2456041